SUMMARY Resting mitochondrial matrix Ca2+ is maintained through a MICU1-established threshold inhibition of MCU activity. It is not known how MICU1 interacts with MCU to establish this Ca2+ threshold for mitochondrial Ca2+ uptake and MCU activity. Here, we show that MICU1 localizes to the mitochondrial matrix side of the inner mitochondrial membrane and MICU1/MCU binding is determined by a MICU1 N-terminal polybasic domain and two interacting coiled-coil domains of MCU. Further investigation reveals MICU1 forms homo-oligomers, and this oligomerization is independent of the polybasic region. However the polybasic region confers MICU1 oligomeric binding to MCU and controls mitochondrial Ca2+ current (IMCU). Moreover, MICU1 EF-hands regulate MCU channel activity but do not determine MCU binding. Loss of MICU1 promotes MCU activation leading to oxidative burden and a halt to cell migration. These studies establish a molecular mechanism for MICU1 control of MCU-mediated mitochondrial Ca2+ accumulation, and dysregulation of this mechanism likely enhances vascular dysfunction.

We sought to analyse the presence of human papillomavirus (HPV), Chlamydia trachomatis and cytomegalovirus (CMV) infection in women with epithelial ovarian carcinomas. Polymerase chain reaction (PCR)-based detection of microbial infections was carried out. A total of 39 tissue samples were analysed with consensus and type-specific primers for HPV, primers specific for the cryptic plasmid of Chlamydia and primers for glycoprotein B of CMV. The samples analysed showed 40%, 80% and 50% positivity for HPV, Chlamydia and CMV infection, respectively, in cancerous ovarian tissues. The HPV type detected was HPV 6, with its genome integrated to the host genome in case of both invasive and borderline tumours and existed episomally in healthy controls. The patients with Chlamydia (odds ratio [OR] 32; 95% confidence interval [CI] 3.33, 307.65) and CMV infection (OR 8; 95% CI 0.888, 72.10) are at significantly higher risk of development of ovarian tumours. The present study validates the theory of chronic infections and inflammation in the pathogenesis of epithelial ovarian cancer. Further seroepidemiological studies and large fresh tissue sampling may represent the real prevalence of infections among ovarian carcinoma patients. This study is the first of its kind in detecting the bacterial and viral aetiologies in the development of ovarian carcinoma among Indian women.

Overall HPV prevalence in 576,281 women was estimated to be 32.1% (95% CI 32.098, 32.102). Corresponding estimates by region showed Eastern Asia (China) with the highest prevalence of about 57.7% of the HPV infection followed by South Central Asia (Indian subcontinent). The HPV prevalence was higher in less developed countries (42.2%) than in more developed regions (22.6%). The type-specific HPV prevalence study showed HPV 16 (9.5%) and 18 (6.2%) to be the prevalent type irrespective of the region of study. First coitus at a younger (≤ 15) age, increased number of pregnancies, increased number of sexual partners, use of contraceptives, smoking and chewing habit and early age at marriage were recognized as the significant risk factors for HPV infection. The phylogenetic analysis of HPV-16 showed the clustering of Indian sequence with the European and American sequences suggesting a similarity between HPV types. Even though the oncogenic proteins of HPV-16 detected in more developed and less developed regions clustered, the prevalence and the severity of the diseases among the less developed regions could be well explained as the exposure of the population to the possible associated risk factors concerning to the living conditions and nature of the life style adopted by the population.

No abstract

The sponge-associated actinomycetes were isolated from the marine sponge Dendrilla nigra, collected from the southwest coast of India. Eleven actinomycetes were isolated depending upon the heterogeneity and stability in subculturing. Among these, Nocardiopsis dassonvillei MAD08 showed 100% activity against the multidrug resistant pathogens tested. The culture conditions of N. dassonvillei MAD08 was optimized under submerged fermentation conditions for enhanced antimicrobial production. The unique feature of MAD08 includes extracellular amylase, cellulase, lipase, and protease production. These enzymes ultimately increase the scope of optimization using broad range of raw materials which might be efficiently utilized. The extraction of the cell free supernatant with ethyl acetate yielded bioactive crude extract that displayed activity against a panel of pathogens tested. Analysis of the active thin layer chromatography fraction by Fourier transform infrared and gas chromatography-mass spectrometry evidenced 11 compounds with antimicrobial activity. The ammonium sulfate precipitation of the culture supernatant at 80% saturation yielded an anticandidal protein of molecular weight 87.12 kDa. This is the first strain that produces both organic solvent and water soluble antimicrobial compounds. The active extract was non-hemolytic and showed surface active property envisaging its probable role in inhibiting the attachment of pathogens to host tissues, thus, blocking host-pathogen interaction at an earlier stage of pathogenesis.